Inclusion of patients with reduced performance status (ECOG 2 or higher) in FDA registrational trials for renal cell carcinoma (RCC).

453 Background: Clinical trials often use performance status indicators to include only those participants with good baseline functional status. The Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) and the Karnofsky Performance Scale (KPS) are two such scales that determine a cancer patient’s ability to perform common tasks. As a result, the study population does not accurately represent the real-world population. We evaluated the inclusion of patients with ECOG 2 or greater/ KPS less than 70 in RCC clinical trials leading to FDA approvals between 2014 and 2024. Methods: The US Food and Drug Administration (FDA) approvals for drugs approved in RCC and associated clinical evidence were collected from the FDA website from 2014-2024. Data from each registrational trial was searched in public databases using drug name, trial name, and registration number. The total number and percentage of participants in each ECOG/KPS category were recorded and analyzed. Results: The FDA approved 13 drugs and combinations for the treatment of RCC from 2014 - 2024. A cumulative total of 8731 participants were included in these trials, with only 24 (0.3%) participants with ECOG PS 2 or greater (KPS <70). Only 3 of the 13 trials included participants with ECOG 2 (KPS <70) with 2 trials having <1% ECOG 2 participants. Only CABOSUN trial had >10% enrolment of ECOG 2 participants. There was no participation of ECOG 3 in any of the trials. Of the total participants, over 70% belonged to ECOG score 0 or KPS 90-100 (excluding CheckMate 214 for which PS distribution data was unavailable). Conclusions: There is poor enrollment of participants with ECOG 2 and greater in registrational clinical trials for RCC. This limits the therapeutic options available for patients with poor PS and is not representative of the real-world population. Greater inclusion of poor PS patients is needed in future trials. Percentage enrollment of patients with reduced PS in registrational trials for RCC. Clinical trial Year Reduced PS% (ECOG 2 or higher/KPS <70) CABOSUN 2017 12.7% S-TRAC 2017 0.2% CheckMate 025 2015 0.4% LITESPARK-005, KEYNOTE-564, TIVO-3, CLEAR, CHECKMATE-9ER, JAVELIN Renal 101, KEYNOTE-426, CheckMate 214, METEOR, Lenvatinib+Everolimus 2016-2023 0.0%